ACTG 366 is a phase I/II, open-label study with a management algorithm design for highly antiretroviral-experienced, HIV-infected children with rapidly progressive or advanced HIV disease for whom current antiretroviral therapy is failing. This protocol evaluates novel combinations of antiretroviral drugs of the reverse transcriptase inhibitor and protease inhibitor classes in reducing viral load, and evaluates the safety and pharmacokinetics of these combinations. The study stipulates that each subject must receive a total of 4 agents, at least 2 of which are novel for the individual patient. The treatment duration is 52 weeks with an option for extension to 100 weeks. This multicenter study is currently open to accrual. To date, 153 patients have been enrolled at all centers (one at CHOP). The target accrual goal is 200 patients nationwide. No preliminary data are available.